Copper-Catalyzed Asymmetric Propargylation of Cyclic Aldimines

The copper-catalyzed asymmetric propargylation of cyclic aldimines is reported. The influence of the imine trimer to inhibit the reaction was identified, and equilibrium constants between the monomer and trimer were determined for general classes of imines. Asymmetric propargylation of a diverse series of N-alkyl and N-aryl aldimines was achieved with good to high asymmetric induction. The utility was demonstrated by a titanium catalyzed hydroamination and reduction to generate the chiral indolizidines (−)-crispine A and (−)-harmicine.

本工作报道了环状醛亚胺（cyclic aldimines）的铜催化不对称炔丙基化反应。研究发现亚胺三聚体对该反应具有抑制作用，并针对几类常见亚胺测定了其单体与三聚体间的平衡常数。针对一系列结构多样的N-烷基醛亚胺与N-芳基醛亚胺，均可实现该不对称炔丙基化反应，且获得了从中等到优异的不对称诱导效果。通过钛催化氢胺化（hydroamination）与还原反应，成功合成了手性吲哚里西啶（indolizidines）类化合物(−)-crispine A与(−)-harmicine，验证了该方法的实用价值。